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体内靶向性和确定性单细胞恶性转化

In vivo targeted and deterministic single-cell malignant transformation.

作者信息

Scerbo Pierluigi, Tisserand Benjamin, Delagrange Marine, Debare Héloise, Bensimon David, Ducos Bertrand

机构信息

Laboratoire de Physique de l'Ecole Normale Supérieure LPENS, ENS, PSL Research University, CNRS, Sorbonne Université, Université de Paris, Paris, France.

Inovarion, Paris, France.

出版信息

Elife. 2025 Mar 25;13:RP97650. doi: 10.7554/eLife.97650.

DOI:10.7554/eLife.97650
PMID:40130618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11936417/
Abstract

Why does a normal cell possibly harboring genetic mutations in oncogene or tumor suppressor genes becomes malignant and develops a tumor is a subject of intense debate. Various theories have been proposed but their experimental test has been hampered by the unpredictable and improbable malignant transformation of single cells. Here, using an optogenetic approach we permanently turn on an oncogene (KRASG12V) in a single cell of a zebrafish brain that, only in synergy with the transient co-activation of a reprogramming factor (VENTX/NANOG/OCT4), undergoes a deterministic malignant transition and robustly and reproducibly develops within 6 days into a full-blown tumor. The controlled way in which a single cell can thus be manipulated to give rise to cancer lends support to the 'ground state theory of cancer initiation' through 'short-range dispersal' of the first malignant cells preceding tumor growth.

摘要

为什么一个可能在癌基因或肿瘤抑制基因中携带基因突变的正常细胞会变成恶性并发展成肿瘤，这是一个激烈争论的话题。人们提出了各种理论，但由于单细胞不可预测且不太可能发生的恶性转化，对这些理论的实验验证受到了阻碍。在这里，我们使用光遗传学方法在斑马鱼大脑的单个细胞中永久激活一个癌基因（KRASG12V），该细胞只有在与重编程因子（VENTX/NANOG/OCT4）的瞬时共激活协同作用下，才会经历确定性的恶性转变，并在6天内强劲且可重复地发展成一个成熟的肿瘤。通过这种可控方式，单个细胞能够被操纵引发癌症，这为“癌症起始的基态理论”提供了支持，该理论认为肿瘤生长之前的第一批恶性细胞通过“短程扩散”形成肿瘤。

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本文引用的文献

1
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Nature. 2024 May;629(8012):688-696. doi: 10.1038/s41586-024-07328-w. Epub 2024 Apr 24.
2
Cancers make their own luck: theories of cancer origins.癌症创造自己的运气：癌症起源理论。
Nat Rev Cancer. 2023 Oct;23(10):710-724. doi: 10.1038/s41568-023-00602-5. Epub 2023 Jul 24.
3
Evaluating cancer etiology and risk with a mathematical model of tumor evolution.运用肿瘤进化的数学模型评估癌症病因和风险。
Nat Commun. 2022 Nov 24;13(1):7224. doi: 10.1038/s41467-022-34760-1.
4
Cell competition in development, homeostasis and cancer.发育、体内平衡和癌症中的细胞竞争
Nat Rev Mol Cell Biol. 2023 Mar;24(3):221-236. doi: 10.1038/s41580-022-00538-y. Epub 2022 Sep 29.
5
The current state of the art and future trends in RAS-targeted cancer therapies.RAS 靶向癌症治疗的现状和未来趋势。
Nat Rev Clin Oncol. 2022 Oct;19(10):637-655. doi: 10.1038/s41571-022-00671-9. Epub 2022 Aug 26.
6
Vertebrate Cell Differentiation, Evolution, and Diseases: The Vertebrate-Specific Developmental Potential Guardians / and / Enter the Stage.脊椎动物细胞分化、进化与疾病：脊椎动物特异性发育潜能守护者/登场。
Cells. 2022 Jul 26;11(15):2299. doi: 10.3390/cells11152299.
7
Fgf8 dynamics and critical slowing down may account for the temperature independence of somitogenesis.Fgf8 动力学和临界减速可能解释了体节发生的温度独立性。
Commun Biol. 2022 Feb 7;5(1):113. doi: 10.1038/s42003-022-03053-0.
8
Hallmarks of Cancer: New Dimensions.癌症的特征：新视角。
Cancer Discov. 2022 Jan;12(1):31-46. doi: 10.1158/2159-8290.CD-21-1059.
9
Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity.脑胶质瘤蛋白质组的地形测绘揭示了肿瘤内异质性的三轴模型。
Nat Commun. 2022 Jan 10;13(1):116. doi: 10.1038/s41467-021-27667-w.
10
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Dev Cell. 2021 Oct 25;56(20):2808-2825.e10. doi: 10.1016/j.devcel.2021.08.018. Epub 2021 Sep 15.